Different regions of the brain must communicate with each other to provide the basis for the integration of sensory information, sensory-motor coordination and many other functions that are critical for learning, memory, information processing, perception and the behaviour of organisms. Hebb suggested that this is accomplished by the formation of assemblies of cells whose synaptic linkages are strengthened whenever the cells are activated or 'ignited' synchronously. Hebb's seminal concept has intrigued investigators since its formulation, but the technology to demonstrate its existence had been lacking until the past decade. Previous studies have shown that very fast electroencephalographic activity in the gamma band (20-70 Hz) increases during, and may be involved in, the formation of percepts and memory, linguistic processing, and other behavioural and perceptual functions. We show here that increased gamma-band activity is also involved in associative learning. In addition, we find that another measure, gamma-band coherence, increases between regions of the brain that receive the two classes of stimuli involved in an associative-learning procedure in humans. An increase in coherence could fulfil the criteria required for the formation of hebbian cell assemblies, binding together parts of the brain that must communicate with one another in order for associative learning to take place. In this way, coherence may be a signature for this and other types of learning.

Transient periods of synchronization of oscillating neuronal discharges in the frequency range 30-80 Hz (gamma oscillations) have been proposed to act as an integrative mechanism that may bring a widely distributed set of neurons together into a coherent ensemble that underlies a cognitive act. Results of several experiments in animals provide support for this idea. In humans, gamma oscillations have been described both on the scalp (measured by electroencephalography and magnetoencephalography) and in intracortical recordings, but no direct participation of synchrony in a cognitive task has been demonstrated so far. Here we record electrical brain activity from subjects who are viewing ambiguous visual stimuli (perceived either as faces or as meaningless shapes). We show for the first time, to our knowledge, that only face perception induces a long-distance pattern of synchronization, corresponding to the moment of perception itself and to the ensuing motor response. A period of strong desynchronization marks the transition between the moment of perception and the motor response. We suggest that this desynchronization reflects a process of active uncoupling of the underlying neural ensembles that is necessary to proceed from one cognitive state to another.

Patients with extensive damage to the right hemisphere of their brain often exhibit unilateral neglect of the left side of space. The spatial attention of these patients is strongly biased towards the right, so their awareness of visual events on the left is impaired. Extensive right-hemisphere lesions also impair tonic alertness (the ability to maintain arousal). This nonspatial deficit in alertness is often considered to be a different problem from spatial neglect, but the two impairments may be linked. If so, then phasically increasing the patients' alertness should temporarily ameliorate their spatial bias in awareness. Here we provide evidence to support this theory. Right-hemisphere-neglect patients judged whether a visual event on the left preceded or followed a comparable event on the right. They became aware of left events half a second later than right events on average. This spatial imbalance in the time course of visual awareness was corrected when a warning sound alerted the patients phasically. Even a warning sound on the right accelerated the perception of left visual events in this way. Nonspatial phasic alerting can thus overcome disabling spatial biases in perceptual awareness after brain injury.

A large proportion of right-hemisphere stroke patients show hemispatial neglect-a neurological deficit of perception, attention, representation, and/or performing actions within their left-sided space, inducing many functional debilitating effects on everyday life, and responsible for poor functional recovery and ability to benefit from treatment. The frequent parietal locus of the lesion producing neglect reflects the impairment of coordinate transformation used by the nervous system to represent extrapersonal space. Given that adaptation to a visual distortion can provide an efficient way to stimulate neural structures responsible for the transformation of sensorimotor coordinates, the aim of our study was to investigate the effect of prism adaptation on various neglect symptoms, including the pathological shift of the subjective midline to the right. All patients exposed to the optical shift of the visual field to the right were improved on their manual body-midline demonstration and on classical neuropsychological tests. Unlike other physiological manipulations used to improve neglect, this improvement lasted for at least two hours after prism removal and thus could be useful in rehabilitation programmes. The positive effect found for both sensorimotor and more cognitive spatial functions suggests that they share or depend on a common level of space representation linked to multisensory integration.

Pheromones are airborne chemical signals that are released by an individual into the environment and which affect the physiology or behaviour of other members of the same species. The idea that humans produce pheromones has excited the imagination of scientists and the public, leading to widespread claims for their existence, which, however, has remained unproven. Here we investigate whether humans produce compounds that regulate a specific neuroendocrine mechanism in other people without being consciously detected as odours (thereby fulfilling the classic definition of a pheromone). We found that odourless compounds from the armpits of women in the late follicular phase of their menstrual cycles accelerated the preovulatory surge of luteinizing hormone of recipient women and shortened their menstrual cycles. Axillary (underarm) compounds from the same donors which were collected later in the menstrual cycle (at ovulation) had the opposite effect: they delayed the luteinizing-hormone surge of the recipients and lengthened their menstrual cycles. By showing in a fully controlled experiment that the timing of ovulation can be manipulated, this study provides definitive evidence of human pheromones.

Since the first report in unicells, studies across diverse species have demonstrated that light is a powerful synchronizer which resets, in an intensity-dependent manner, endogenous circadian pacemakers. Although it is recognized that bright light (approximately 7,000 to 13,000 lux) is an effective circadian synchronizer in humans, it is widely believed that the human circadian pacemaker is insensitive to ordinary indoor illumination (approximately 50-300 lux). It has been proposed that the relationship between the resetting effect of light and its intensity follows a compressive nonlinear function, such that exposure to lower illuminances still exerts a robust effect. We therefore undertook a series of experiments which support this hypothesis and report here that light of even relatively low intensity (approximately 180 lux) significantly phase-shifts the human circadian pacemaker. Our results clearly demonstrate that humans are much more sensitive to light than initially suspected and support the conclusion that they are not qualitatively different from other mammals in their mechanism of circadian entrainment.

Substantial evidence from animal studies suggests that enhanced memory associated with emotional arousal results from an activation of beta-adrenergic stress hormone systems during and after an emotional experience. To examine this implication in human subjects, we investigated the effect of the beta-adrenergic receptor antagonist propranolol hydrochloride on long-term memory for an emotionally arousing short story, or a closely matched but more emotionally neutral story. We report here that propranolol significantly impaired memory of the emotionally arousing story but did not affect memory of the emotionally neutral story. The impairing effect of propranolol on memory of the emotional story was not due either to reduced emotional responsiveness or to nonspecific sedative or attentional effects. The results support the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system.

Advances in the understanding of molecular biology of human disease and the development of efficient gene transfer techniques have resulted in practical approaches to human gene therapy, with new techniques being developed at an increasing rate. The first trials have now begun in humans and initial results are positive.